Association between environmental contaminants and health outcomes in indigenous populations of the Circumpolar North

Figures & data

Fig. 1.  Studies by health category.

Fig. 2.  Studies by health category and location.

Fig. 3.  Studies by contaminant.

*OCPs – e.g. p,p′-DDE, DDT, HCB, PCP.

**PFCs – e.g. PFOA, PFOS.

***Other – octachlorostyrene, dioxin-like compounds, POPs (specific compounds unspecified).

Cd=cadmium; DDE=dichlorodiphenyldichloroethylene; DDT=dichlorodiphenyltrichloroethane; HCB=hexachlorobenzene; Hg=mercury; OCPs=organochlorine pesticides; Pb=lead; PBDEs=polybrominated diphenyl ethers; PCBs=polychlorinated biphenyls; PCP=pentachlorophenol; PFCs=perfluorinated compounds; PFOA=perfluorooctanoic acid; PFOS=perfluorooctanesulfonate; POPs=persistent organic pollutant.

Table I. Paediatric studies

Study	Contaminant	Outcome	Population	Results*
Infections
Jensen (19)	PCBs and OCPs	Otitis media	Mother–child pairs (n=400) and children 4–10 years of age at follow-up (n=223) (participation rate: 56%)	No association
Dallaire (20)	PCBs	Acute respiratory infection	Children 0–5 years of age (n=343) (participation rate: 70%)	Cord PCB-153 • Acute otitis media: RR=1.37, 95% CI: 1.20–1.55 • LRTI: RR=1.44, 95% CI: 1.20–1.72 • URTI or hospitalization: No association
Dallaire (21)	PCBs and p,p′-DDE	Acute infections	Infants during the first 12 months of life (n=199)	Maternal PCB-153 • LRTI (first 6 months): RR=1.68, 95% CI: 1.00–2.81 (3rd exposure quartile) • GI infection (12 months): RR=1.59, 95% CI: 1.01–2.49 (3rd exposure quartile) Maternal p,p′-DDE • URTI (first 6 months): RR=1.56, 95% CI: 1.05–2.33 (2nd exposure quartile) • URTI (12 months): RR=1.34, 95% CI: 1.00–1.78 (2nd exposure quartile) • Otitis media (first 6 months): RR=1.83, 95% CI: 1.09–3.07 (3rd exposure quartile) • All infections (first 6 months): RR=1.33, 95% CI: 1.03–1.73 (3rd exposure quartile) • GI infection (12 months): RR=1.59, 95% CI: 1.03–2.47 (2nd exposure quartile) Child PCB or p,p′-DDE: No association
Dewailly (22)	PCBs and OCPs	Infections and immune status	Newborns followed up to 12 months of age (n=171)	Breast milk Mirex • Acute otitis media (4–7 months): RR=1.88, 95% CI: 1.14–3.08 (2nd exposure tertile) Breast milk dieldrin • Acute otitis media (4–7 months): RR=1.75, 95% CI: 1.05–2.91 (3rd exposure tertile) Breast milk HCB • Acute otitis media (first 12 months): RR=1.49, 95% CI: 1.10–2.03) (3rd exposure tertile) Breast milk p,p′-DDE • Acute otitis media (first 12 months): RR=1.52, 95% CI: 1.05–2.22) (3rd exposure tertile) Breast milk PCBs: No association Bronchopulmonary diseases: No association Immunological parameters: No association
Behavioural
Boucher (27)	PCBs, Hg and Pb	ADHD	Children followed from birth to 11 years of age (n=279) (participation rate: 95%)	Cord Hg • Attention problems: Positive association (β=0.13, 95% CI: 0.00–0.25) • Disruptive Behaviour Disorders score:  OR=2.87, 95% CI: 1.04–7.94 (ADHD-inattentive type, 3rd exposure tertile)  OR=2.92, 95% CI: 1.07–8.04 (ADHD-hyperactive impulsive type, 3rd exposure tertile)
				Child blood Pb • Externalizing problems: Positive association (β=0.14, 95% CI: 0.01–0.26) • Disruptive Behaviour Disorders score:  OR=5.52, 95% CI: 1.38–22.12 (ADHD-hyperactive impulsive type, 3rd exposure tertile) PCB-153: No association
Verner (28)	PCBs	Attention and activity	Infants followed from birth to 11 months of age (n=168)	Cord PCB-153 • Inattention: Positive association (Spearman's correlation=0.205) Infant blood PCB-153 • Non-elicited activity: Positive association (Spearman's correlation=0.182 at 11 months of age)
Plusquellec (29)	PCBs, Hg and Pb	Behavioural indicators	Children followed from birth to 5 years of age (n=110)	Cord PCB-153 • Happiness: Inverse association (β=−0.22) • Anxiety: Positive association (β=0.26) • Global activity latency: Inverse association (β=−0.25) • Positive affect rate: Inverse association (β=−0.24) Child blood Pb • Impulsivity: Positive association (β=0.20) • Irritability: Positive association (β=0.20) • Inattention: Positive association (β=0.21) Hg: No association
Plusquellec (35)	Pb	Behavioural function	Infants 11 months of age (n=169)	Cord Pb • Frenetic activity: Associated with greater activity (β=−0.16) • Off-task duration: Positive association (β=0.17) • Off-task latency: Inverse association (β=−0.20) No association with other measures
Fraser (36)	Pb	Motor function and behaviour	Children 5 years of age (n=110)	Child blood Pb • Impulsivity: Positive association (Pearson correlation=0.25) • Activity: Positive association (Pearson correlation=0.25) No association with attention level
Neurological
Ethier (23)	PCBs, Hg and Pb	Visual brain development	Children followed from birth to 10–13 years of age (n=172)	Cord Hg • N75 amplitude at 95% contract level: Positive association (β=0.206) • N75 latency at 12% contrast level: Positive association (β=0.285) Cord Pb • N150 latency: Positive association (β=0.238, 0.209, 0.251 at 95%, 12% and 4% contrast levels respectively) PCB-153: No association
Boucher (24)	PCBs	Response inhibition error monitoring	Children followed from birth to a mean age of 11 years (n=196)	Child plasma PCB-153 • Reaction times: Positive association (i.e. slower times) (β=0.18 for go trials) • Amplitudes of Pe and Pc response-related potentials: Inverse association (β=−0.16 and −0.20 respectively) Cord Pb: • Correct responses: Inverse association (i.e. fewer correct responses) (β=−0.21 and −0.17 for correct go and no-go responses respectively) Child blood Pb • Correct responses on no-go trials (false alarms): Inverse association (more false alarms) (β=−0.16) • P3 amplitudes: Inverse association (β=−0.16 and −0.23 for go and no-go trials respectively Hg: No association
Boucher (25)	PCBs and Hg	Information processing	Children followed from birth to 11 years of age (n=118)	Cord PCB: No association with sample as a whole • P3b amplitude in subgroup of children breast-fed for >3 months: Inverse association (β=−0.32) Cord Hg • Reaction times: Positive association (i.e. slower time) (β=0.15) • False alarms: Inverse association (i.e. fewer false alarms) (β=−0.21) • N1 latency: Positive association (β=0.29) • N1 amplitude: Inverse association (β=−032)
Boucher (32)	Pb	Working memory	Children 5 years of age (n=104) or 11 years of age (n=201) (participation rate: 26% for ERP at 5 years and 55% for ERP at 11 years)	Cord Pb (5 years) • P3b amplitude: Inverse association (β=−0.38) Child blood Pb (5 years) • P3b latency: Positive association (β=0.37) Pb (11 years): No association
Saint-Amour (33)	PCBs and Hg	Visual brain processing	Children followed from birth to 5–6 years of age (n=102)	Child plasma PCB-153 • P100 latency at 95% contrast: Positive association (β=2.50) • N150 latency at 12% contrast: Positive association (β=5.58) • N75–P100 amplitude at 95% contrast: Inverse association (β=−3.74) Cord Hg • P100 latency at 30% contrast: Positive association (β=3.34) Child blood Hg • N75 early latency at 95% and 30% contrasts: Inverse association (β=−3.90 and −3.18, respectively) • P100 latency at 95% and 30% contrasts: Inverse association (β=−3.26 and −3.94, respectively)
Després (26)	PCBs, Hg and Pb	Neuromotor functions	Children followed from birth to pre-school (n=110)	Child plasma PCB-153 • Sway oscillations: Positive association (β=0.22 for transversal sway) Child blood Hg • Tremor: Positive association (β=0.20) Child blood Pb • Reaction time: Positive association (i.e. slower time) (β=0.24) • Sway oscillations: Positive association (β=0.24, 0.22, 0.26 for velocity, sagittal and transversal sway) • Movement irregularity: Positive association (β=0.22) • Coherence between hands: Inverse association (β=−0.29) • Synkinesis: Positive association (β=0.23) • Tremor: Positive association (β=0.24)
Weihe (34)	Hg	Neurobehavioural performance	Children followed from birth to 7–12 years of age (n=21) and children 7–12 years of age (n=22)	Maternal hair Hg • Hand–eye coordination (error score): Positive association (r=0.44) Peak latencies on brainstem auditory evoked potentials prolonged at higher exposure levels when data combined with other cohorts (Faroes and Madeira)
Cardiovascular and endocrine
Valera (31)	Hg	Blood pressure and heart rate variability	Children followed from birth to 11 years of age (n=226) (participation rate: 46%)	Child blood Hg • HRV – low frequency: Inverse association (β=−0.24) • HRV – SDNN: Inverse association (β=−0.28) • HRV – SDANN: Inverse association (β=−0.32) • HRV – CVRR: Inverse association (β=−0.06) Blood Pressure: No association
Sandau (30)	PCBs, PCP and octachlorostyrene	Thyroid function	Newborns (n=10)	Cord PCP • T3, TBG and fT4: Inverse association (r=−0.55, −0.44, −0.51 respectively) Cord ΣPCBs and ΣPCB hydroxylated metabolites • TSH: Inverse association (r=−0.46 and −0.45 respectively) Sum of all cord chlorinated phenolic compounds • T3 and fT4: Inverse association (r=−0.48 and −0.47 respectively)

ADHD=attention deficit hyperactivity disorder; CI=confidence interval; CVRR=coefficient of variation of R-R intervals; DDE=dichlorodiphenyldichloroethylene; ERP=event-related potential; fT₄=free thyroxine; GI=gastrointestinal; HCB=hexachlorobenzene; Hg=mercury; HRV=heart rate variability; LRTI=lower respiratory tract infection; OCPs=organochlorine pesticides; OR=odds ratio; Pb=lead; PCBs=polychlorinated biphenyls; PCP=pentachlorophenol; RR=relative risk; SDANN=standard deviation of R-R intervals measured over 5 min periods; SDNN=standard deviation of R-R intervals; T₃=triiodothyronine; TBG=thyroxine-binding globulin; TSH=thyroid-stimulating hormone; URTI=upper respiratory tract infection

*Adjusted estimates are presented where available. Presented estimates are statistically significant at p≤0.05 level.

Table II. Studies of reproductive health

Study	Contaminant	Outcome	Population	Results*
Mocevic (53)	Hg	Semen quality and reproduc. hormones	Male partners of pregnant women (n=194)	Inhibin B: Positive association (β=0.074, 95% CI: 0.021–0.126) No association with other semen characteristics or reproductive hormones
Kvist (54)	PFOA and PFOS	Sperm Y:X ratio	Male partners of pregnant women (n=201) (participation rate: 78.5%)	PFOS • Inverse association (i.e. lower Y:X ratio) (β=−0.002, 95% CI: −0.004–0.000) • PFOA: No association
Krüger (37)	PCBs and OCPs	ER, AR and AhR function	Men and women (n=247) (participation rate: 41% of all Greenlandic AMAP population and 74% for XAR and XAR comp outcomes)	ΣPCBs • ER transactivity (males): Inverse association (β=−0.36 and −0.24 for XER and XERcomp respectively) • ER transactivity (females): Inverse association (β=−0.41 for XERcomp) • AhR transactivity (males): No association • AhR transactivity (females): Inverse association (β=−0.61) • ΣOCPs ER transactivity (males): Inverse association (β=−0.34 for XER) • ER transactivity (females): Inverse association (β=−0.36 for XERcomp) • AhR transactivity (males): Inverse association (β=−0.29) • AhR transactivity (females): Inverse association (β=−0.55) • AR transactivity: No association
Krüger (38)	PCBs and OCPs	ER and AR transactivity	Men and women (n=240) (participation rate: 82% for XAR/XER outcome)	ΣPCBs • ER transactivity (males and females): No association upon adjustment • AR transactivity (males): Inverse association (β=−0.42) • AR transactivity (females): No association ΣOCPs • ER transactivity (males): No association • ER transactivity (females): Inverse association when adjusted for age (β=−0.24) • AR transactivity (males): Inverse association (β=−0.36) • AR transactivity (females): No association
Bonde (43)	PCBs and p,p′-DDE	Fertility and markers of male reproductive function	Pregnant women and their spouses (n=598) (participation rate: 90%)	PCB-153 • LH: Positive association (β=0.07, 95% CI: 0.02–0.12) • Sperm volume: Inverse association (β=−0.11, 95% CI: −0.2 to −0.04) • Progressive sperm: Inverse association (β=−4, 95% CI: −6 to −1) • Sperm counts: Low counts in subgroup of men with short androgen receptor CAG repeat length • Neutral α-glucosidase activity in seminal plasma: Inverse association • (β=−0.1, 95% CI: −0.2 to −0.0) • No association with other measures (e.g. time to conceive, apoptotic markers, sperm chromatin integrity)
				p,p′-DDE • Inhibin B: Positive association (β=6.4, 95% CI: 1.7–13.8) • Free testosterone: Positive association (β=0.02, 95% CI: 0.0–0.04) • Sperm volume: Inverse association (β=−0.04, 95% CI: −0.16 to −0.01) • Progressive sperm: Inverse association (β=−0.01, 95% CI: unclear to −0.6) • No association with other measures (e.g. sperm chromatin integrity, apoptotic markers, epididymal and accessory sex gland function)
Krüger (50)	POPs (evaluated as effects on ER, AR and AhR)	Sperm chromatin integrity	Male spouses of pregnant women (n=53)	• DNA fragmentation index: Inverse association with ER and AhR activities • DNA stainability: No association
Long (39)	PCBs and OCPs	AhR transactivity	Men and women 18–77 years of age (n=357) (participation rate: 48% for AhR comp outcome)	ΣPCBs: • No association (males or females) with AhR-TEQ • Inverse association with AhRcomp in males and females combined (β=−0.18) ΣOCPs • Inverse association with AhR-TEQ (β=−0.31) in males; No association in females • Inverse association with AhR-TEQ (β=−0.21) in males and females combined • Inverse association with AhRcomp in males and females combined  (β=−0.18)
Krüger (40)	PCBs and p,p′-DDE	Serum xenoandrogenic activity	Male spouses of pregnant women (n=37)	PCB-153: No association • p,p′-DDE: No association
Toft (52)	POPs (evaluated as effects on ER, AR and AhR)	Semen quality	Male spouses of pregnant women (n=54)	No association specifically in Inuit. When data combined across all 4 populations (Warsaw, Greenland, Kharkiv, Sweden), ER activity associated with increase in sperm concentration and motility.
Long (51)	POPs (evaluated as effects on ER, AR and AhR)	Sperm DNA damage and Sperm apoptotic markers	Male spouses of pregnant women (n=54)	DNA damage: Inverse association with ER and AhR Bcl-xL marker: Inverse association with AR (Spearman's correlation=−0.46) No association with the sperm apoptotic marker, Fas
Long (41)	PCBs and p,p′-DDE	AhR activity	Males (n=75)	PCB-153: No association p,p′-DDE: No association
Stronati (45)	PCBs and p,p′-DDE	Sperm DNA fragmentation and sperm apoptotic markers	Male spouses of pregnant women (n=200) (participation rate: 79%)	PCB-153: No association p,p′-DDE: No association
Elzanaty (47)	PCBs and p,p′-DDE	Epididymal function and Accessory sex gland function	Male spouses of pregnant women (n=163)	PCB-153 • Epididymal marker (neutral-α glucosidase): Inverse association (β=−0.2, 95% CI: −0.3 to −0.04) • No association with PSA, zinc, or fructose p,p′-DDE: No association
Giwercman (48)	PCBs and p,p′-DDE	Reproductive hormone levels	Male spouses of pregnant women (n=258) (participation rate: 79%)	PCB-153 • LH: Positive association for highest exposure group compared with lowest exposure group (MD=1.4 IU/L, 95% CI: 1.1–1.7 IU/L) • No association with other reproductive hormones p,p′-DDE • Free testosterone: Positive association (β=0.011, 95% CI: 0.004–0.024) • Inhibin B: Positive association for highest exposure group compared with lowest exposure group (MD=35 ng/L, 95% CI: 1.5–69 ng/L) • No association with other reproductive hormones
Bonefeld-Jorgensen (42)	PCBs and p,p′-DDE	Serum xenoestrogenic activity	Male spouses of pregnant women (n=72)	PCB-153: No association p,p′-DDE: Inverse association (Spearman's correlation=−0.29 for XER)
Tiido (49)	PCBs and p,p′-DDE	Sperm Y:X ratio	Male spouses of pregnant women (n=157)	PCB-153: No association p,p′-DDE: No association
Toft (44)	PCBs and p,p′-DDE	Fertility	Pregnant women (n=598) and their spouses (n=201) (participation rate: 87%)	PCB-153: No association p,p′-DDE: No association
Spanò (46)	PCBs and p,p′-DDE	Sperm chromatin integrity	Male spouses of pregnant women (n=193)	PCB-153: No association p,p′-DDE: No association

AhR=aryl hydrocarbon receptor; AMAP=Arctic Monitoring Assessment Programme; AR=androgen receptor; CI=confidence interval; DDE=dichlorodiphenyldichloroethylene; DNA=deoxyribonucleic acid; ER=oestrogen receptor; Hg=mercury; IU=international unit; LH=luteinizing hormone; MD=mean difference; OCPs=organochlorine pesticides; PCBs=polychlorinated biphenyls; PFOA=perfluorooctanoic acid; PFOS=perfluorooctanesulfonate; POPs=persistent organic pollutants; PSA=prostate specific antigen.

*Adjusted estimates are presented where available. Presented estimates are statistically significant at p≤0.05 level.

Table III. Studies of obstetrics and gynaecology

Study	Contaminant	Outcome	Population	Results*
Dallaire (55)	PCBs, HCB and Hg	Foetal Growth and pregnancy duration	Pregnant women (n = 248) (participation rate: 59%)	Cord PCB-153, HCB and Hg • Duration of pregnancy: Inverse association (β = − 0.17 to −0.20) • Fatal growth (mediated through shorter gestation period): Inverse association for length (β = − 0.16 to −0.18 for PCB-153 and HCB respectively)
Wojtyniak (56)	PCBs and p,p′-DDE	Birth weight, gestational age and preterm birth	Women with singleton live births (n = 572) (participation rate: 86%)	PCB-153 • Birth weight: Inverse association (β = − 59.2, 95% CI: −100.6 to −17.8) • Gestational age: Inverse association (β = − 0.2, 95% CI: −0.4–0.0) p,p′-DDE • Birth weight: Inverse association (β = − 39.4, 95% CI: −79.0–0.2) • Gestational age: Inverse association (β = − 0.2, 95% CI: −0.4–0.0) No association with preterm birth
Dallaire (57)	PCBs, HCB and PCP	Thyroid hormone levels	Pregnant women (n = 107) and infants up to 7 months of age (n = 130)	Thyroid hormone levels in women at delivery:  Maternal PCB hydroxylated metabolites • T3: Positive association (β = 0.57) • No association with other thyroid hormones  Maternal PCB-153, HCB and PCP: No association Thyroid hormone levels in umbilical cord:  Maternal and cord PCB-153 • TBG: Inverse association (β = − 0.25 for maternal PCB-153 and −0.26 for cord PCB-153) • No association with other thyroid hormones  Maternal PCP • fT4: Inverse association (β = − 0.59) • No association with other thyroid hormones  Maternal or cord HCB and PCB hydroxylated metabolites/cord PCP: No association Infant PCB-153 or HCB: No association
Toft (58)	PCBs and p,p′-DDE	Menstrual cycle	Pregnant women presenting for antenatal care at local hospitals (n = 454) (participation rate: 90%)	PCB-153 • Long menstrual cycles: Inverse association (OR = 0.7, 95% CI: 0.5–0.96) • No association with average cycle length, irregular cycles, or short cycles p,p′-DDE • Long menstrual cycles: Inverse association (OR = 0.7, 95% CI: 0.5–0.99) • No association with average cycle length, irregular cycles, or short cycles
Lucas (59)	PCBs and Hg	Birth weight and gestational age	Pregnant women (n = 491) (participation rate: 30% for gestational age outcome)	Cord PCB-153 • Birth weight: Positive association in unadjusted analysis Hg: No association
Muckle (60) (Abstract only)	PCBs, OCPs and Hg	Developmental effects	Not provided	OCs • Physical growth at birth: Inverse association (estimate not provided) • Duration of pregnancy: Inverse association (estimate not provided) Hg: No information provided
Pereg (61)	PCBs	Placental CYP1A1 activity	Pregnant women admitted to hospital upon delivery (n = 35)	No association
Lagueux (62)	PCBs and OCPs	Placental CYP1A1 activity and DNA adducts	Women giving birth in regional hospitals (n = 22)	PCB-153, p,p′-DDE, HCB • CYP1A1 activity: Positive association in moderate smokers (R^2=0.21, 0.51, 0.38 respectively) PCB-118 • CYP1A1 activity: Positive association in heavy smokers (R^2=0.30) • Associated with bulky DNA adduct formation in non-smokers and moderate smokers across all cohorts, including non-Inuit p,p′-DDE • Associated with less bulky DNA adducts across all cohorts, including non-Inuit
Foldspang (63)	Hg	Gestational length and birth weight	Mothers with singleton deliveries (n = 376) (participation rate: 45.9% newborns represented from one district)	Birth weight: Inverse association (β = − 7.1 for maternal blood mercury and −4.2 for offspring blood mercury) No association with gestational length

CI = confidence interval; DDE = dichlorodiphenyldichloroethylene; DNA = deoxyribonucleic acid; fT₄=free thyroxine; HCB = hexachlorobenzene; Hg = mercury; OCs = organochlorines; OCPs = organochlorine pesticides; OR = odds ratio; PCBs = polychlorinated biphenyls; PCP = pentachlorophenol; T₃=triiodothyronine; TBG = thyroxine-binding globulin.

*Adjusted estimates are presented where available. Presented estimates are statistically significant at p ≤ 0.05 level.

Table IV. Studies of cardiology, endocrinology, bone health, oncology and oxidative stress in adults

Study	Contaminant	Outcome	Poulation	Results*
Cardiology
Valera (64)	PCBs and OCPs	Hypertension (≥140/90 mm Hg or taking anti-hypertensive medication)	Men and women ≥18 years of age (n=1,614) (participation rate: 52% from larger population)	ΣDL-PCBs • Hypertension: Positive association in youngest age category (18–39 years) (OR=1.34, 95% CI: 1.03–1.74) Σnon-DL-PCBs • Hypertension: Inverse association in oldest age category (≥40 years) (OR=0.81, 95% CI: 0.66–0.99) DDT • Hypertension: Positive association in youngest age category (18–39 years) (OR=1.42, 95% CI: 1.08–1.85) Aldrin, α-chlordane, γ-chlordane • Hypertension: Inverse associations in youngest age category (18–39 years) (OR=0.39, 95% CI: 0.20–0.78; OR=0.38, 95% CI: 0.19–0.75;  OR=0.10, 95% CI: 0.03–0.38 respectively) Mirex • Hypertension: Inverse association in oldest age category (≥40 years)  (OR=0.80, 95% CI: 0.69–0.93) No association across all age categories
Valera (65)	Hg	Blood pressure, resting heart rate and pulse pressure	Men and women ≥18 years of age (n=313) (participation rate: 41%)	Resting heart rate: Positive association Diastolic blood pressure: Inverse association No association with systolic blood pressure or pulse pressure
Nielsen (66)	Hg	Blood pressure	Men and women 30–69 years of age (n=1,861) (participation rate: 67.5%)	Diastolic blood pressure: Inverse association in men (β=−0.04) Hypertension: Inverse association in men (OR=0.99, 95% CI: 0.98–0.99) No association in women
Valera (67)	Hg	Blood pressure	Men and women ≥18 years of age (n=732) (participation rate: 55%)	Systolic blood pressure: Positive association (β=2.14, 95% CI: 0.94–3.33) Diastolic blood pressure: No association
Château-Degat (70)	PFOS	Plasma lipids	Men and women 18–74 years of age (n=723) (participation rate: 68%)	Triacylglycerol: Inverse association in women (β=−0.0014) HDL-C: Positive association (β=0.0042 and 0.0016 for women and men respectively) Ratio TC/HDL-C: Inverse association (β=−0.0035) No association with LDL-C or non-HDL-C
Valera (68)	Hg	Blood pressure and cardiac autonomic activity	Men and women ≥40 years of age (n=280) (participation rate: 59%)	SDANN: Inverse association (β=−0.086, 95% CI: −0.16 to −0.01) Systolic blood pressure: Positive association (β=4.77, 95% CI: 1.12–8.42) Pulse pressure: Positive association (β=3.40, 95% CI: 1.11–5.69) No association with diastolic blood pressure or other measures of cardiac autonomic activity
Luoma (69)	Cd	Blood pressure and arterial hypertensive disease	Reindeer herders 20–82 years of age in Arctic Finland (n=230) (participation rate: 14%)	Systolic blood pressure: Positive association Diastolic blood pressure: No association
Endocrinology
Jørgensen (71)	PCBs and OCPs	Glucose intolerance	Men and women (mean age 49 years) (n=692) (participation rate: 67%)	PCBs and OCPs 2-hour insulin: Inverse association DL-PCBs and non-DL-PCBs HOMA-B: Inverse association. No association with mean fasting glucose, mean 2-hour glucose, or mean fasting insulin. No association with IGT or diabetes.
Dallaire (72)	PCBs, OCPs, PBDEs, PFOS and dioxin-like compounds	Thyroid function	Men and women ≥18 years of age (n=623) (participation rate: 50%)	PCBs T3: Inverse association (β=−0.020) (inverse association also for PCB metabolites) TBG: Inverse association (β=−0.037) (inverse association also for PCB metabolites) HCB T3: Inverse association (β=−0.030) fT4: Inverse association (β=−0.017) TBG: Inverse association (β=−0.054) β-HCH T3: Inverse association (β=−0.028) TBG: Inverse association (β=−0.051) PFOS T3: Inverse association (β=−0.017) fT4: Positive association (β=0.014) TBG: Inverse association (β=−0.034) TSH: Inverse association (β=−0.102) No associations with p,p′-DDE or PBDEs after full adjustment for confounders
Bone health
Paunescu (73)	DL-PCBs (evaluated as effects on AhR)	Bone strength	Women 35–72 years of age (n=194)	No association
Côté (74)	PCBs and OCPs	Bone ultrasound	Peri- and post-menopausal women 49–64 years of age (n=153)	PCB-156 • Broadband ultrasound attenuation (indication of bone density and architecture): Inverse association (β=−8.12) • Speed of sound (indication of bone density and elasticity): Inverse association (β=−22.68) • Stiffness index (indication of rigidity of bone structure): Inverse association (β=−11.95) PCB-153: No association
Oncology
Bonefeld-Jorgensen (75)	PCBs, OCPs, PFCs and heavy metals	Breast cancer	Cases (n=31) and controls (n=115)	PCBs • Highest quartile of exposure significantly higher for cases than controls. Otherwise no association.
				PFCs • Positive association with breast cancer (OR=1.03, 95% CI: 1.001–1.07 for PFOS and 1.03, 95% CI: 1.00–1.05 for Σperfluorosulfonated acids) ΣPOPs • Positive association (OR=1.02, 95% CI: 1.01–1.04) OCPs: No association Heavy metals: No association
Rusiecki (76)	PCBs and OCPs	DNA methylation (Alu and LINE-1 assays)	Mostly males 19–67 years of age (n=70)	ΣPCBs • Inverse association on Alu assay (β=−0.56) (i.e. DNA hypomethylation) p,p′-DDE, DDT, other pesticides • Inverse associations on Alu assay (β=−0.26 to −0.75) ΣPOPs • Inverse association on Alu assay (β=−0.48) No association on LINE-1 assays
Other
Bélanger (78)	PCBs and Hg	Oxidative stress (redox status of CoQ10 and vitamin E)	Men and women (majority women) (n=99)	ΣPCBs • Total tocopherols: Positive association (β=2.68) • α-Tocopherol: Positive association (β=4.12) • Ratio α-tocopheryl quinone/α-tocopherol: Inverse association (β=−0.41) • Overall, no evidence of oxidative stress Hg • α-Tocopheryl quinone: Inverse association (β=−0.30) • Overall, no evidence of oxidative stress No association with ubiquinol-10 or ubiquinone-10 and PCBs or Hg
Bélanger (77)	PCBs and Hg	Oxidative stress (plasma oxidized LDL-C, homocysteine, glutathione peroxidase, glutathione reductase and glutathione)	Men and women (majority women) (n=99)	PCBs • Oxidized LDL-C: Positive association (β=0.11) Hg: No association

AhR=aryl hydrocarbon receptor; Cd=cadmium; CI=confidence interval; DDE =dichlorodiphenyldichloroethylene; DDT=dichlorodiphenyltrichloroethane; DL-PCBs=dioxin-like polychlorinated biphenyls; DNA=deoxyribonucleic acid; fT₄=free thyroxine; HCB=hexachlorobenzene; HCH=hexachlorocyclohexane; HDL-C=high density lipoprotein cholesterol; Hg=mercury; HOMA-B=homeostasis model assessment of beta cell function; IGT=impaired glucose tolerance; LDL-C=low density lipoprotein cholesterol; OCPs=organochlorine pesticides; OR=odds ratio; PBDEs=polybrominated diphenyl ethers; PCBs=polychlorinated biphenyls; PFCs=perfluorinated compounds; PFOS=perfluorooctanesulfonate; POPs=persistent organic pollutants; SDANN=standard deviation of the average RR intervals calculated over 5 minute periods; T₃=triiodothyronine; TBG=thyroxine-binding globulin; TC=total cholesterol; TSH=thyroid-stimulating hormone.

*Adjusted estimates are presented where available. Presented estimates are statistically significant at p≤0.05 level.

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